Researchers have been developing antimicrobial treatments and agents for decades. Recently, there has been a need for new antimicrobial agents for treating an increasing number of drug-resistant bacterial, viral, and fungal infections.
Various bioactive peptides have been reported in both the scientific literature and in issued patents. Peptides historically have been isolated from natural sources, and have recently been the subject of structure-function relationship studies. Additionally, natural peptides have served as starting points for the design of synthetic peptide analogs.
Various patents exist describing cosmetic compositions containing short peptides. For example, U.S. Pat. No. 6,492,326 suggests the preparation and use of skin care compositions containing pentapeptides and skin care active ingredients.
Strom et al. 2003 (Journal of Medicinal Chemistry 46: 1567-1570) describe short antibacterial peptides focused mainly on very short peptides (dimers and trimers) containing chemical modifications. Certain hexapeptides are also described. However, there is no testing or discussion of antimicrobial activity of these hexapeptides.
Alpha-melanocyte-stimulating hormone (α-MSH) is a 13-amino acid neuropeptide with potent anti-inflammatory activity. It is produced by posttranslational processing of the larger precursor molecule pre-opiomelanocortin. The carboxy-terminal tripeptide of α-MSH, comprising of residues 11 to 13, KPV, has been demonstrated to exert anti-inflammatory activity in vivo and in vitro (Brzoska, T., Luger, T A. et al., α-melanocyte-stimulating hormone and related tripeptides: biochemistry, anti-inflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocrine Reviews 2009. 29 (5): 581-602). A structurally related derivative, KdPT (KPT) has been described to be collinear to residues 193-195 of IL-1β and seem to be capable of interacting with the IL-1 receptor type I (Luger T. A., and Brzoska T. α-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann Rheum Dis 2007; 66 (suppl III): iii52-iii55). There was one report suggesting that KPV has antimicrobial influence on S. aureus and C. albicans, but no MIC was determined (Cutuli M et al., 2000, antimicrobial effects of α-MSH peptides, J. Leukocyte Biology, 67:233-239). Unlike KPV, KdPT tripeptide has never been reported to possess antimicrobial influence.
Thus, there is a need to develop peptides having a broad range of potent antimicrobial activity against a number of microorganisms, including gram negative and gram positive bacteria. Cost of manufacture of antimicrobial peptides is also a key consideration to pharmaceutical and cosmetic applications. We disclose in this invention a cost effective short antimicrobial peptides that can be used in pharmaceutical or cosmetic compositions for topical treatment or management of skin conditions associated with bacterial and fungal infections.